Japan Pushing Forward In Global Scrum For Cancer Leads
This article was originally published in PharmAsia News
Executive Summary
Japan is forging ahead with a national project to elucidate cancer-related gene alterations in its population, both to identify responder patients for possible inclusion in clinical trials for targeted therapies and to inform the development of new treatments.
With the Rugby World Cup getting underway in the UK, it seems appropriate to be talking about scrums, particularly after the Japanese team’s historic last-minute upset of past winners South Africa. Japanese scientists are hoping they can be as successful in another battle, this time not involving the "Brave Blossoms" but rather a team of industry and academic researchers tackling cancer.
The collaborative SCRUM-Japan cancer genome screening initiative, led by Japan's National Cancer Center (NCC), began in 2013 as part of a broader strategic push into individualized medicine research. There is broad participation by the local pharma industry in the project, whose partners include Takeda Pharmaceutical Co. Ltd., Astellas Pharma Inc. and Daiichi Sankyo Co. Ltd., along with multinationals Pfizer Inc. and AstraZeneca PLC.
By the end of 2014, 188 medical institutions nationwide and around 1,400 patients had been enrolled in the SCRUM-Japan project, which is building a database of its findings. In May this year, Takeda also signed a linked agreement with the NCC to discover and develop novel and improved anticancer agents through joint basic research on disease pathogenesis and the sharing of information and researchers.
Addressing the recent IBC Oncology Asia meeting in Tokyo, Dr. Atsushi Ohtsu, director of the NCC's Exploratory Oncology Research & Clinical Trial Center (EPOC), said that the SCRUM program practically started two important new projects - on lung and gastrointestinal cancer screening - earlier this year, under which it is aiming to gather 4,500 samples over two years.
“The hope is to identify more data on the incidence of disease-related genes,” including for example ALK/RET/ROS1 mutations in non-squamous non-small cell lung cancer (NSCLC), to help support the development of appropriate therapies for rarer types of cancer gene alterations, Ohtsu said.
Speaking at the same meeting, Dr. Takashi Kohno, who is involved in translational research at EPOC, noted that the project should also better elucidate some of the oncogene differences there are between Japan and the west.
For instance, while the ALK/RET/ROS1 gene aberrations occur similarly in lung adenocarcinomas in east Asian and US/European patients, EGFR mutations tend to higher - 40-55% versus 5-15% - and KRAS mutations lower (8-10% vs 20-30%).
With around 1,500 patients now enrolled in the pan-Japan screening program for RET fusion-positive NSCLC, the results so far show this type occurs in around 3% of cases, which is in line with the west, Kohno noted.
These results have already facilitated enrollment of likely responder patients in the local LURET trial for the multi-kinase inhibitor vandetinib (AstraZeneca). Meanwhile, the elucidation of ROS1-positive patients – around 4% of all NSCLC patients - has also led to enrollment of selected patients in an ongoing east Asian trial for Pfizer's dual ALK/ROS1 inhibitor Xalkori (crizotinib).
On the gastrointestinal cancer side, 14 pharma firms are now involved in SCRUM-Japan’s genomic screening project, the findings from which are already guiding planned trials for colorectal and other GI cancers at the NCC, Ohtsu told the IBC meeting.
For instance, candidate trials for colorectal cancer patients carrying the BRAF V600E mutation are being planned by the NCC using a combination of dabrafenib (Novartis AG's BRAF inhibitor Tafinlar), panitumumab (Amgen Inc.'s EGFR inhibitor Vectibix) and trametinib (Novartis’s MEK inhibitor Mekinist).
A combination of Tafinlar and Mekinist was granted a positive approval opinion in the EU in July for metastatic melanoma with the BRAF V600 mutation, an indication for which the US FDA has granted priority review.
Combo Approach Key
In line with pharma companies’ existing strategies in the burgeoning immuno-oncology space, Ohtsu told the IBC conference that "combination therapies are key" to success in the field, if efficacy and survival benefits are to be maximized.
A broad range of combinations are now being pursued by most multinationals active in oncology and checkpoint inhibitors, with the initial focus being on the PD-1/PD-L1 space.
In Japan, Ohtsu pointed in particular to original work being performed with a new combination of Kyowa Hakko Kirin Co. Ltd.'s commercialized anti-CCR4 antibody mogamulizumab with Ono Pharmaceutical Co. Ltd.‘s/Bristol-Myers Squibb Co.'s PD-1-targeting antibody Opdivo (nivolumab) in solid tumors.
In the meantime, the academic sector is also conducting early stage basic research on new candidates including an anti-CD4 antibody that has already shown promising results in combination with a PD-1-targeting antibody, and for which clinical studies are planned, the researcher noted.